1. Field of the Invention
The present invention relates to a peptide separated from the fraction of the oyster enzyme hydrate displaying the ability of suppressing angiotensin converting enzyme (ACE) and a pharmaceutical composition for the prevention and treatment of cardiovascular disease comprising the said peptide as an active ingredient.
2. Description of the Related Art
According to the rapid economic development, the pattern and the aspect of disease have also been changed, so that cardiovascular disease is remarkably increasing, for example arteriosclerosis, hypertension, angina pectoris, myocardial infarction, ischemic heart disease, heart failure, complications caused by transluminal coronary angioplasty, cerebral infarction, cerebral hemorrhage, and stroke are in increase. According to the ranking of cause of death reported by Statistics Korea in 2010, cardiovascular disease is ranked as the second topmost cause of death in Korea, which is next to malignant tumor. Particularly, death rate of cardiovascular disease is significantly increased in male over 55 years of age and in female over 65 years of age.
The most representative cardiovascular disease, hypertension, takes 15˜20% of total adult disease, making it a world-wide health issue. Even though there is no specific symptoms in hypertension patients, it is highly required to control and treat the disease because the risk of the same complications as shown in other cardiovascular diseases such as arteriosclerosis, stroke, myocardial infarction and end-stage renal disease is still high. Hypertension is a chronic disease that requires life-long treatment, suggesting that social and economical loss is great.
The cause of hypertension is still unknown, but is presumed to be developed by genetic factors such as family history, races, salt intake, insulin resistance, and obesity and/or environmental factors such as excessive drinking and aging, etc. Among many factors that are involved in raising blood pressure, renin-angiotensin-aldosterone cycle has been known to play an important role in regulating blood pressure and body fluid level in vivo (Weiss, D. et. al (2001) Circulation 103: 448-454).
In particular, renin-angiotensin system (RAS) has been known to play an important role in the development of essential hypertension which takes 80% of total hypertension cases. In general, renin-angiotensin system is activated when the blood flow rate or sodium level is dropped in the kidney or when the activity of sympathetic nervous system is increased. Renin secreted in juxtaglomerular cells in renal artery decomposes angiotensin into angiotensin I and then angiotensin I is converted into angiotensin II inducing the contraction of blood vessel by angiotensin converting enzyme (ACE). As a result, angiotensin II regulates blood pressure by increasing aldosterone synthesis and by neuroregulation. ACE also decomposes bradykinin having vasodilating activity so as to inactivate bradykinin.
Therefore, angiotensin converting enzyme inhibitor (ACE inhibitor) is expected to be able to treat or prevent cardiovascular diseases such as hypertension, heart disease, arteriosclerosis, or cerebral hemorrhage, considering that ACE has a great effect on blood pressure increase, on which therefore studies have been focused. Particularly, various clinical attempts have been made to confirm if the decrease of the cases and even the death rate of chronic kidney disease, arteriosclerosis, and heart attack could be achieved by such ACE inhibitor and the results thereby have been reported.
Based on the above reports, chemically synthesized angiotensin converting enzyme inhibitors such as ramipril, captopril, enarapil, risinopril, fosinoril, and spirapril are commercialized and used as hypertension treating agents. However, these compounds are so easily decomposed in a pharmaceutical administration form, that means stability is low, and they cause side effects by affecting other cells including weakness of whole body, vomiting, cough, headache, anorexia, and taste disorder, etc. (Lim S D. et. al (2008) Korean J. Food Sci. Ani. Resour, 28(5): 587-595). Thus, it is required to develop a natural ACE inhibitor that has increased stability but has less side effects in vivo.
Oyster, nicknamed “the milk from the ocean,” has been known as an excellent health food. Even in Western countries, where live sea food is not eaten as often as in Asian countries, live oyster is eaten. As nutrition factors, oyster contains glycogen, taurine, protein, vitamin, and various minerals, making an excellent substance for health food. Oyster is also effective in strengthening the functions of heart and liver, in treating hypertension and arteriosclerosis, and in preventing heart disease. Since oyster contains a plenty of selenium, it not only has detoxication activity for heavy metals but also is known as the tonic and stamina food increasing the functions of heart, liver, pancreas, and other organs.
As for the known natural ACE inhibitors so far, Korean Patent Publication No. 10-2012-0092735 describes the composition for inhibiting angiotensin converting enzyme, or having antihypertensive or antidiabetic property, comprising Capsosiphon fulvescens extract treated by enzyme. Korean Patent No. 10-1275766 describes the composition for inhibiting angiotensin converting enzyme, or having antihypertensive or antiobese property, comprising protein extract of abalone intestine
The peptides having ACE inhibiting activity have been identified from the enzyme hydrolysates of natural substances. Among them, valine-tyrosine, the peptide originated from sardine protein has been confirmed to have the activity of reducing blood pressure in mild hypertension patients (Shimizu, M (1994) Melbourne Sept, 18), because of which it has been approved as the first individual case-authorized health food in Korea. Korean Patent No. 10-1106303 describes the ACE inhibiting activity of the peptide prepared from oyster. However, the need for the development of natural substance derived functional peptides is still in increase.
Therefore, the present inventors tried to identify a peptide having ACE inhibiting activity from the enzyme hydrolysates of natural substances. As a result, the present inventors obtained a novel peptide having ACE inhibiting activity by extracting, separating, and purifying the peptide from oyster enzyme hydrate. Thereafter, the present inventors completed this invention by confirming that the novel peptide identified by the inventors had the effect of regulating blood pressure and of preventing hypertension thereby so that the peptide separated from oyster enzyme hydrate could be effectively used as an active ingredient of a pharmaceutical composition for the prevention or treatment of cardiovascular disease.